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NEUROCHEMICAL STUDIES OF CNS CARDIOVASCULAR CENTERS

中枢神经系统心血管中心的神经化学研究

基本信息

批准号：
3347396
负责人：
ANDREJ ROTTER
金额：
$ 7.44万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 1991-03-31
项目状态：
已结题

项目摘要

There are several drugs currently used to treat hypertension which appear to act on the cardiovascular control centers of the central nervous system. Such drugs include clonidine and Alpha-methyldopa, both of which are Alpha2-adrenergic receptor agonists. Other CNS receptors may also be involved in hypertensive states and their identity might lead to the development of new anti-hypertensive drugs. We wish to study the distribution of five neurotransmitter and their corresponding receptors in central nervous system cardiovascular control centers (for example, the nucleus ambiguus, nucleus of the Xth nerve, nucleus of the solitary tract and the intermediolateral column of the spinal cord), in order to determine which drugs may potentially act at these sites. Markers for adrenergic, cholinergic, gamma-aminobutyric acid, glutamate, and serotonin transmission and their receptors will be detected by light microscope histochemistry and autoradiography. Receptor concentrations of cardiac and vasomotor control centers in adult rats will also be determined after deafferentation and axotomy. The changes observed will indicate whether the receptors tested are localized pre- or postsynaptically. In addition, the concentration of neurotransmitter and drug receptors in the cardiovascular control centers of neonatal and adult normotensive and spontaneously hypertensive rats will be compared. This comparison might reveal the chemical nature of central transmitter system malfunction underlying hypertension.

目前有几种药物用于治疗高血压作用于中枢神经的心血管控制中心系统。这类药物包括可乐定和α-甲基多巴，这两种药物都是是α2肾上腺素能受体激动剂。其他中枢神经系统受体也可能以及他们的身份可能会导致开发新的降压药。我们希望研究一下 5种神经递质及其相应受体在大鼠脑内的分布中枢神经系统心血管控制中心(例如，疑核、第X神经核、孤束核和脊髓中间外侧柱)，以便确定哪些药物可能在这些部位起作用。肾上腺素能的标志物，胆碱能、γ-氨基丁酸、谷氨酸和5-羟色胺传递它们的受体将通过光学显微镜组织化学和放射自显影。心脏和血管运动控制的受体浓度成年大鼠的中枢也将在去传入和轴突切断术。观察到的变化将表明接受测试的受体在突触前或突触后被本地化。此外，浓缩物的浓度心血管控制中心的神经递质和药物受体新生和成年正常血压和自发性高血压大鼠被比较。这种比较可能揭示CENTER的化学性质传导系统故障是高血压的潜在原因。